Table 2.
Studies identifying dormancy-associated/regulating genomic signatures
| Tumor type | Samples | Host | Primary tumor site | In vivo dormancy model | Genomic analysis | Signatures | References |
|---|---|---|---|---|---|---|---|
| Breast | Human ER+ (MCF7, T47D, Pt. samples); TN (MDA-MB-231, Pt. samples) | SCID | Orthotopic | FACS isolation of Cell Trace Violet-retaining cells from orthotopic tumor | Affimetrix microarray (HG-U133A/B) | Upregulated: ACVR1, ADAM10, AMOT, BHLHE41, COL1A1, COL4A5, CTSD, DDR1, EPHA5, GATA6, HIST1H2BK, IGFBP5, MMP2, NR2F1, P2HA1, SOX9, SREBF1, STAT3, TGFB2, THBS1, TP53, TPM1 Downregulated: APEX1, ASNS, ATF3, ATF4, BUB1, BUB1B, CDKN3, CENPB, CKS2, DNMT1, DTYMK, EGFR, EGR1, ESM1, FOSL1, FOXD1, FOXM1, IGFR1, IL8, JUN, MMP1, NT5E, ODC1, PIK3CB, PLAT, TIMP3, TK1 |
[84] |
| Breast | Human PDXs: HCI-001, HCI-002, HCI-010 | NOD/SCID | Orthotopic | Early-stage (low burden) vs. late-stage (high burden) metastases in lung, LN, BM, liver, brain | Fluidigm 96.96 qPCR DynamicArray chips | Upregulated: TGFR2, BCL2L1, EPHA4, AR, LGR5, IGFBP6, TGFB2, SOX2, BMI1, CXCL12, TWIST1, BCL2, NOTCH4, KRT5, POU4F1, TGFB1, THY1, CDKN1B, WNT2, SKP2, DAND5, PGR, CHEK1, CDJ3, MTOR, TP73, TGFBR3, ESR2, ESR1, MAX, NTRK2, NOTCH3, FIGF, MME, TP63, TP53, MYCN, SNAI2, ITGA6, JAG1, ACTA2 Downregulated: PTEN, TGFBR1, ERBB3, CDH1, CDK2, MUC1, VEGFA, CAV2, MYC, ITGB1, PARP2, EMP1, CD24, VIM |
[85] |
| Breast | Mouse 4TO7 cells | BALB/c | IV | Infection of dormant 4TO7 cells with a retroviral cDNA library from macrometastasis-forming 4T1 tumors or with mouse-specific shRNA library; isolation of lung metastases. | PCR identification of transduced cDNAs or shRNAs in metastatic cells | cDNAs that drive metastasis: Tm4sf1, Dand5, Mrpl3, Malat1 shRNAs that drive metastasis: Cart1, Pcna, Nek4, Cd3g, Itga3, Numb, Pdcd5, Smyd5, Smurf2, Ebrbb4, Gfg2, Gpr34, Il2, Lyn, March5, Sfrs6, Shbg, Src, Yes1 |
[86] |
| Prostate | Human Pt. DTCs | Humans | N.A. | Isolation of EpCAM+/CD45- DTCs from Pts with PSA rise after radical prostatectomy, but no evidence of disease | Agilent microarray array | Upregulated: SMAD7, KRT18, CDKN2C, CDKN2B, CDKN1A, TGIF1, RXRA, NR2F1, ACVR1, COL4A5, DDR1, HIST1H2BK, IGFBP5, P4HA1, SREBF1, STAT3, TGFB2, THBS1, TP53, TPM1, BMP7, BHLHE41, HSPA5, HSP90B1, PDIA3, PPIB Downregulated: APEX1, ATF3, ATF4, BUB1, BUB1B, CDKN3, CEBPG, DNMT1, DTYMK, EGR1, FOXD1, FOXM1, IGF1R, IL8, JUN, NT5E, ODC1, PIK2CB, PLAT, ESM1, MMP1 |
[29] |
| Pancreas | Mouse Ink4a.1 cells | FVB | Orthotopic | Isolation of luciferase-positive liver DTCs or macrometastases after primary tumor resection | 10X Genomics scRNA-seq | Upregulated: Fam167b, Clec1b, Apoa2, Clec4f, Alb, Cldn5, Gm21320, Xcl1, Dnase1l3, Clec14a, Gpr182, Jchain, Ccl5, Ly6d, Gzma, Cd300lg, Apoc1, Adgr14, Robo4, Fabp1, Esam, Kdr, Bmp2, Gm21762, Fam174b, Cd5l, Apoa1, Gpihbp1, Slc40a1, Cyp4b1, Rapgel5, Vsig4, Egfl7, Stab2, btnl9, nkg7, tff2, tspan7, Calcrl, Gimap7, Selenop, Cd55, Apoe, Hspa1a, Gimap6, Mzb1, Ppp1r16b Downregulated: Tagln, Tpm2, Gpx8, Crct1, Prrx2, Timp1, Lox, Grem1, Fn1, Prl2c2, Ak1, Col8a1, Actg2, Ankrd1, Ltbp1, Prkg2, Cthrc1, Tnn2, Ociad2, Col5a2, Phlda3, Prrx1, Cemip |
[87] |
| Multiple sites | Human and mouse | N.A. | N.A. | Analysis of 10 datasets yielding 21 comparisons between cancer vs. dormancy conditions to produce a dormancy-interaction network | multiple platforms | AKAP12, CD44, CDKN1A, DDR1, EPAS1 GSN, HBP1, IL1B, NDRG1, NOTCH3, PLAUR, SMAD3, THBS1, TIMP2, TSC22D3 | [88] |
| Breast | MCF-7, SK-BR-3, MDA, MB-468, MDA-MB-231 | N.A. | N.A. | Selection for quiescent BrCa cells: retention of lipophilic dye Vybrant DiD after 6 passages in vitro | Illumina RNA-seq | CCL5, CCN3, CDH11, COL17A1, FPR3, HMGCS2, IGFBP5, KLK8, MGAM, MUC5AC, OASL, PLAT, PTGFR, PTGS2, PTPRH, PTPRN2, RSAD2, SERPINA1, SERPINA3, SERPINE1, TNFRSF10C, VWA5A | [89] |
| Breast | Mouse PyMT-Bo1; D2A1 & D2.0R | C57BL6/J; BALB/cJ | IC, IT | Isolation of tetracycline-induced H2B-mCherry+ BrCa cells in collagenase-digested bone; single cells isolated by FACS | Illumina scRNA-seq | CFH, GAS6, MME, OGN, POSTN, PDGFRB, DHRS3, MGP, ALDH1A1, ALDH3A1, PRELP, AAK1, THBD, BCL2L11, GLIS1 | [90] |
| Breast | Mouse MMTV-Wnt1/iFG-FRR1 | FVB.rGH-luc-GFP | Orthotopic | Minimal residual disease/quiescence: treatment of tumored mice with the FGFRi, NVP-BGJ398 for 14d. 2 weeks off drug, recurrent tumors isolated 1–4 months later | 10X Chromium scRNA-seq | Dormancy Upregulated: Notch3, Aph1b, Dll1, Mfng, Hes7, Sox9, Snai2, Hes1 Downregulated: Psenen, Got1 Recurrence Upregulated: Rita1, Psen1, Adam17, Kat2b, Tgfb2, Gata2, Snai1 Downregulated: Trp63, Hes1, Fbwx7, Stat1 |
[91] |
N.A., not applicable